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Öğe Curcumin Acts as Post-protective Effects on Rat Hippocampal Synaptosomes in a Neuronal Model of Aluminum-Induced Toxicity(Springer/Plenum Publishers, 2019) Kar, Fatih; Hacıoğlu, Ceyhan; Uslu, Sema; Kanbak, GüngörThe neurotoxic effects of aluminum are generally associated with reduced antioxidant capacity, increased oxidative stress and apoptosis, which lead to the induction of neurodegenerative processes. Curcumin has a lipophilic polyphenol character and effects of antioxidant and anti-apoptotic. The present study was undertaken to examine possible aluminum exposure in rats brain synaptosomes and to investigate whether protective and therapeutic effects of curcumin on biochemical and morphological changes in both pre- and post-treated groups. Aluminum chloride (AlCl3) at 50 mu M concentration and curcumin at 5 and 10 mu g/mL doses were applied to hippocampal synaptosomes of rats according to experimental design. Biochemical effects were evaluated by MTT cytotoxicity, malondialdehyde (MDA) levels, nitric oxide (NO) levels, glutathione (GSH) levels, caspase 3 activities, cytochrome c levels, DNA fragmentation values and protein levels. Morphological examinations were done by TEM analysis. AlCI3 exposure in the synaptosomes enhanced oxidative stress, triggered apoptosis and caused ultrastructural alterations which were well reflected in the TEM images. Curcumin pre-treatment slightly ameliorated the MDA levels, NO levels, cytochrome c levels and caspase 3 activities in AlCI3-exposed synaptosomes, but these results were not statistically significant. Furthermore, curcumin post-treatment significantly improved oxidative damage and morphological alterations, and suppressed cytochrome c and caspase 3 activities. Taken together, our data showed that curcumin had more therapeutic effects than protective effects in AlCI3-induced neurotoxicity. Nevertheless, the therapeutic (post-protective) effects of curcumin should be further investigated in in vivo neurodegenerative models involving behavioral tests.Öğe Curcumin and LOXblock-1 ameliorate ischemia-reperfusion induced inflammation and acute kidney injury by suppressing the semaphorin-plexin pathway(Pergamon-Elsevier Science Ltd, 2020) Kar, Fatih; Hacioglu, Ceyhan; Senturk, Hakan; Donmez, Dilek Burukoglu; Kanbak, Gungor; Uslu, SemaAims: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. Main methods: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 mu g/kg, i.p.). Key findings: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-alpha, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. Significance: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.Öğe Obezite ACSL4 ve GPX4 Aracılı Ferroptozis ile Oksidatif Stresi İndükler(2022) Sezgin, Gülay; Kar, Fatih; Hacıoğlu, Ceyhan; Uslu, SemaBu çalışmada, vücut kitle indeksine (VKİ) göre oluşturulmuş yetişkin bireylerden oluşan deney gruplarında oksidatif stres belirteçleri ve ferroptoz parametreleri toplam 39 yetişkin birey normal kilolu veya hafif kilolu (VKİ:18.5-29.9), birinci derece obez (VKİ 30-34.9) ve ikinci derecede obez (VKİ:35-39,9) olmak üzere on üçer kişilik üç gruba ayrılmıştır. Kontrol grubundaki sağlıklı bireylerin ve obezite gruplarındaki hastaların serum örneklerinden malondialdehit (MDA) ,total antioksidan kapasite (TAS), total oksidan kapasite (TOS), glutatyon (GSH), asil-CoA sentetaz uzun zincirli aile üyesi 4 (ACSL4) ve glutatyon peroksidaz 4 (GPx4) seviyeleri ölçülmüştür. TOS seviyeleri, kontrol grubu ile karşılaştırıldığında 1. derece obez ve 2. derece obez hastalarda artarken (p<0.0001) TAS seviyeleri, 1. derece obez ve 2. derece obez hastalarda azalmıştır (p<0.001). MDA seviyeleri, kontrol grubuna kıyasla 1. derece obez (p<0,001) ve 2. derece obez hastalarda(p <0,0001) artmıştır. GSH seviyeleri ise obezite derecesi arttıkça düşüş göstermiştir (p<0.001). Kontrol grubuna kıyasla 1. derece obez ve 2. derece obez hastaların ACSL4 seviyeleri artış gösterirken (p<0.001), GPx4 seviyeleri her iki obez gupta da azalmıştır (p<0.001). Obezite derecesi arttıkça lipit peroksidasyonu ve oksidatif stres artmaktadır. Ek olarak kontrol grubuna kıyasla obez bireylerde GPx4 seviyelerinin azalışı ve ACSL4 seviyelerinin artışı birlikte değerlendirildiğinde obezitenin ferroptozu indüklediği düşünülebilir.